Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: tetramer assay and therapeutic implications

• Published in: Journal of biomedical science Vol. 10; no. 1; pp. 120 - 135
• Main Authors: Tsai, Sun-Lung, Sheen, I-Shyan, Chien, Rong-Nan, Chu, Chia-Min, Huang, Hsiu-Chu, Chuang, Yen-Ling, Lee, Tzong-Hsien, Liao, Shuen-Kuei, Lin, Chen-Lung, Kuo, George C, Liaw, Yun-Fan
• Format: Journal Article
• Language: English
• Published: England 01.01.2003
• Subjects: Adult; Aged; Antigens, Viral - immunology; Antiviral Agents - pharmacology; CD8-Positive T-Lymphocytes - immunology; Cytokines - immunology; Epitopes - immunology; Female; Hepatitis B - drug therapy; Hepatitis B - immunology; Hepatitis C - drug therapy; Hepatitis C - immunology; Humans; Immunity, Cellular - drug effects; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Male; Middle Aged; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 1021-7770; 1423-0127
• DOI: 10.1007/bf02256004

Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p = 0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.